Topical composition containing antioxidants

ABSTRACT

Disclosed herein are compositions for topical application that effectively deliver antioxidants across the epidermis, dermis, or a combination thereof into cells and/or the bloodstream while concurrently maintaining chemical activity of the antioxidants. In certain aspects, these formulations include emulsions and balms each having a lipophilic carrier and a lipophilic antioxidant solubilized by the lipophilic carrier. Also disclosed herein are methods for making these compositions for topical application.

CROSS-REFERENCE TO RELATED APPLICATION

This Application claims priority to U.S. Provisional Patent ApplicationNo. 62/051,534 filed on Sep. 17, 2014, the contents of which areincorporated by reference herein in their entirety.

TECHNICAL FIELD

The present invention relates generally to the field of compositions fortopical applications, and more particularly, to compositions havinglipophilic, phenolic antioxidants.

BACKGROUND OF THE INVENTION

Reactive Oxygen Species (ROS) are chemically reactive molecules, whichinclude oxygen, superoxides, and various peroxides (e.g., O₂, O₂—, O₂²⁻, peroxy radicals, H₂O₂, etc.). In mammals, ROS are generated (1) as anatural by-product of oxidative metabolism, (2) in response toenvironmental stress, or (3) a combination thereof. Although ROS can bea natural by-product of cellular processes, ROS include free radicalsthat can damage cells by inducing deleterious chemical reactions andcell-signaling pathways. For example, in humans, these ROS-inducedchemical reactions and cell-signaling pathways are often associated withaging, apoptosis (programmed cell death), and illnesses (e.g., variousskin conditions and autoimmune disorders including psoriasis, amytrophiclateral sclerosis, multiple sclerosis, muscular dystrophy, etc.).

Although ROS are associated with inducing deleterious cellularprocesses, numerous cellular defense mechanisms in humans exist tominimize damage often associated with ROS. For example, human cellsinclude various enzymes such as alpha-1-microglobulin, superoxidedismutases, catalases, lactoperoxidases, glutathione peroxidases andperoxiredoxins, which essentially convert potentially harmful ROS andfree radicals into potentially useful chemical molecules that may bere-used by a cell during various cellular processes. For example, FIG. 1illustrates one such endogenous biochemical pathway in which ROS (i.e.,O₂—) is chemically modified by superoxide dismutase into hydrogenperoxide (H₂O₂), and hydrogen peroxide is subsequently converted byglutathione peroxidase into water (H₂O). Thus, FIG. 1 clearly depicts anexemplary, endogenous biochemical pathway in which a cell naturallydefends against ROS and free radicals by converting potentially harmfulO₂ and H₂O₂ into H₂O.

Although FIG. 1 illustrates natural defense mechanisms against ROS,these endogenous natural defense mechanisms can become overwhelmedduring times of increased cellular stress (e.g., times of increasedoxidative metabolism or times of increased environmental stress), whichcan lead to the increased presence of ROS. Likewise, when a person isdeficient in certain enzymes that counteract ROS, ROS can be found inincreased cellular levels within these particular individuals.

Due to the deleterious processes (e.g., aging, apoptosis, etc.) andillnesses associated with increased levels of ROS, supplementation withsubstances that counteract ROS and the deleterious processes anddiseases associated therewith has long been sought. For example, manybelieve that supplementation with vitamins and various antioxidants maybeneficially counteract the deleterious processes associated with ROS.In theory and further based on in vitro experimentation, it is knownthat antioxidants can act as hydrogen donors to ROS (e.g., peroxyradicals) to essentially neutralize free radicals. Based on this theory,it is further thought that antioxidants are viable substances topotentially minimize the effects of ROS in vivo.

While supplementation with antioxidants seems like a viable option tominimize the deleterious effects associated with ROS, numerous problemscurrently exist with such supplementation. For example, many antioxidantformulations are designed for oral administration (e.g., in pill,tablet, or capsule form). However, these oral formulations areineffective because the vast majority of these orally administeredantioxidants are rendered inactive by chemical degradation occurringeither in the stomach or duodenum before being absorbed into the bloodstream. Thus, for at least this reason, oral administration ofantioxidants (via pills, tablets, or capsules) is ineffective.

In addition to oral antioxidant formulations mentioned above, certaintransdermal and transmucosal antioxidant formulations also exist.However, similar to the oral formulations mentioned above, thesetransdermal and transmucosal formulations also have numerous problems.For example, many of these transdermal and transmucosal formulationsinclude hydrophilic, lipophobic antioxidants. Because of the inherentchemical properties of the hydrophilic, lipophobic antioxidants includedwithin these transdermal and transmucosal formulations, theseantioxidants are solvated in water-based solutions (or an aqueous, waterphase of specific formulation). Because these hydrophilic, lipophobicantioxidants are solvated in water-based solutions, crossing lipophilicbiological membranes, such as mucous membranes or the epidermis/dermis,poses a major problem. Specifically, efficient delivery of theseantioxidants poses a major problem due to the high lipid content ofthese membranes. For at least this reason, current transdermal andtransmucosal formulations that administer the above-describedantioxidants are ineffective.

BRIEF SUMMARY OF THE INVENTION

Therefore, a need exists to provide a composition that effectivelydelivers antioxidants while avoiding the degradative processes discussedabove. More particularly, a need exists to provide a transdermalformulation that effectively delivers antioxidants across the epidermis,dermis, or a combination thereof into cells and/or the bloodstream whileconcurrently maintaining chemical activity of these antioxidants.Provided herein are compositions for topical application thateffectively deliver antioxidants across the epidermis, dermis, or acombination thereof into cells and/or the bloodstream while concurrentlymaintaining the antioxidant's chemical activity.

In certain aspects, these formulations include emulsions for topicalapplication. These emulsions may include a water phase ranging 60-90%,65-85%, or 70-80% of the overall emulsion, and an oil phase. The oilphase may include, for example, a lipophilic carrier and a lipophilicantioxidant solubilized by the lipophilic carrier, and the lipophiliccarrier and the lipophilic antioxidant being present from 1:1 to 20:1,1:1 to 15:1, 1:1 to 10:1, 1:1 to 5:1, 1:1 to 3:1, or 1:1 to 2:1 oflipophilic carrier to lipophilic antioxidant in the emulsion. Thelipophilic antioxidant includes one of the following formulas (I) to(III):

In this aspect, R₁ represents a C₁ to C₉ linear or branched alkyl group,styrene, or H. R₂ is optional and represents a C₁ to C₆ linear orbranched alkyl group, styrene, or H. Y₁ represents a C₁ to C₆ linear orbranched alkyl group, H, styrene, —SR₅, or —(CH₂)_(n)COOR₆. R₃ and R₄independently represent a C₁ to C₆ branched alkyl or H. Y₂ represents aC₁ to C₆ linear or branched alkyl group, —SR₅, or —(CH₂)_(n)COOR₆, or H.Y₃ represents a linear or branched alkyl group. “n” is from 1 to 10. R₅represents H, isoprene, a methyl group, an ethyl group, a propyl, abutyl, a pentyl group, a hexyl group, an isopropyl group, an isobutylgroup, a sec-butyl group, a tert-butyl group, a tert-pentyl group, aneo-pentyl group, an isopentyl group, an isohexyl group, a neohexylgroup, styrene, or

R₁₁, R₁₂, and R₁₃ independently represent OH, a methyl group, ethylgroup, a propyl group, a butyl group, an isopropyl group, a tert-butylgroup, an isoprene, tert-pentyl group, or H. R₆ represents an alkylgroup having C₁₀ to C₃₀, and wherein formulas (I) to (III) includepharmaceutically acceptable salts thereof.

In this aspect, the C₁ to C₆ linear or branched alkyl groups of Y₁ andY₂ are substituted with

wherein:

R₇ represents

wherein:

R₈, R₉, and R₁₀ independently represent OH, a methyl group, ethyl group,a propyl group, a butyl group, an isopropyl group, a tert-butyl group,an isoprene, a tert-pentyl group, or H;

at least one of R₈, R₉, and R₁₀ is OH; and

R₈, R₉, and R₁₀ can be in any of the ortho, meta, and para positionsrelative to each other.

In certain aspects, the emulsion includes at least two lipophilicantioxidants from formulas (I) to (III).

In certain aspects, the emulsion includes at least three lipophilicantioxidants from formulas (I) to (III).

In certain aspects, the lipophilic carrier and the lipophilicantioxidant are present from 1:1 to 20:1, 1:1 to 15:1, 1:1 to 10:1, 1:1to 5:1, 1:1 to 3:1, or 1:1 to 2:1 of lipophilic carrier to lipophilicantioxidant in the emulsion.

In certain aspects, the oil phase ranges from 10-40 wt % of the overallemulsion.

In certain aspects, the oil phase ranges from 15-30 wt % or 20-25 wt %of the overall emulsion.

In certain aspects, the lipophilic carrier includes at least one of amineral oil, vegetable oil, or combinations thereof.

In certain aspects, the mineral oil is a paraffinic oil, a naphthenicoil, or a combination thereof.

In certain aspects, the lipophilic carrier includes at least oneselected from the group consisting of argan oil, avocado oil, babassuoil, canola oil, coconut oil, hemp seed oil, jojoba oil, olive oil, androsehip oil.

In certain aspects, the lipophilic carrier is avocado butter, mangobutter, shea butter, cocoa butter, or any combination thereof.

Further disclosed is a balm that is substantially similar to thedisclosed emulsions. However, unlike the disclosed emulsions, the balmpreferably limits the amounts and/or excludes water within its overallcompositions. The balm preferably limits water within its overallcomposition to include as little as 5 wt % water, 3 wt % water, 1 wt %water, 0.5 wt % water, or no water.

Additionally disclosed are methods of making the emulsions and balms.

Additional features, aspects and advantages of the invention will be setforth in the detailed description which follows, and in part will bereadily apparent to those skilled in the art from that description orrecognized by practicing the invention as described herein. It is to beunderstood that both the foregoing general description and the followingdetailed description present various embodiments of the invention, andare intended to provide an overview or framework for understanding thenature and character of the invention as it is claimed. The accompanyingdrawing is included to provide a further understanding of the invention,and are incorporated in and constitute a part of this specification.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other features, aspects and advantages of the presentinvention are better understood when the following detailed descriptionof the invention is read with reference to the accompanying drawing, inwhich:

FIG. 1 illustrates an exemplary, endogenous biochemical pathwaychemically modifying ROS.

DETAILED DESCRIPTION OF THE INVENTION

The present invention will now be described more fully hereinafter. Itis to be understood that the aspects described below are not limited tospecific compounds, synthetic methods, or uses as such may, of course,vary. It is also to be understood that the terminology used herein isfor the purpose of describing particular aspects only and is notintended to be limiting. However, the invention may be embodied in manydifferent forms and should not be construed as limited to therepresentative embodiments set forth herein. The exemplary embodimentsare provided so that this disclosure will be both thorough and complete,and will fully convey the scope of the invention and enable one ofordinary skill in the art to make, use and practice the invention.

Concentrations, amounts, and other numerical data may be expressed orpresented herein in a range format. It is to be understood that such arange format is used merely for convenience and brevity and thus shouldbe interpreted flexibly to include not only the numerical valuesexplicitly recited as the limits of the range, but also to include allthe individual numerical values or sub-ranges encompassed within theranges as if each numerical value and sub-range is explicitly recited.As an illustration, a numerical range of “about 1 to 5” should beinterpreted to include not only the explicitly recited values of about 1to about 5, but also include individual values and sub-ranges within theindicated range. Thus, included in this numerical range are individualvalues such as 2, 3, and 4 and sub-ranges such as from 1-3, from 2-4,and from 3-5, etc. as well as 1, 2, 3, 4, and 5, individually. The sameprinciple applies to ranges reciting only one numerical value as aminimum or a maximum. Furthermore, such an interpretation should applyregardless of the breadth of the range or the characteristics beingdescribed.

It is understood that any given particular aspect of the disclosedcompositions and methods can be easily compared to the specific examplesand embodiments disclosed herein. By performing such a comparison, therelative efficacy of each particular embodiment can be easilydetermined. Particularly preferred compositions and methods aredisclosed in the Examples herein, and it is understood that thesecompositions and methods, while not necessarily limiting, can beperformed with any of the compositions and methods disclosed herein.

Emulsions and Balms

Disclosed are emulsions and balms for topical applications thateffectively deliver antioxidants. More particularly, these emulsions andbalms are transdermal formulations that deliver lipophilic antioxidantsacross the epidermis, dermis, or a combination thereof into a subject'scells and/or the bloodstream while concurrently maintaining chemicalactivity of these antioxidants. “Emulsions” as defined refer tocompositions having a mixture of two phases (e.g., an oil-in-water phaseor a water-in-oil phase). As disclosed further below, the emulsions mayinclude additional solvents and surfactants to maintain a homogenousdispersion of the two phases within the emulsion. In the disclosedemulsions, the water phase of the emulsion includes a majority of water,which includes greater than 50% water, greater than 60% water, greaterthan 70% water, greater than 80% water. or greater than 90% water, andin certain aspects, the overall water content within the disclosedemulsions may include 30-75 wt %, 35-60 wt %, or 45-55 wt % of theoverall weight of the emulsion. In certain aspects, surfactants (e.g.,nonionic surfactants, anionic surfactants, cationic surfactants, or anymixture thereof) are present in an operable concentration of 2-20 wt %,2-10 wt %, 3-10 wt %, 3-8 wt % of the overall emulsion with thepreferable concentration being approximately 3-6% “Balm” as definedherein refers to a composition that omits the addition of water exceptfor the presence of any residual impurities within the composition. Forexample, the balms herein may include as little as 5 wt % water, 3 wt %water, 1 wt % water, 0.5 wt % water, or no water in the overallconcentration of the balm.

In certain aspects, the disclosed emulsions and balms each includelipophilic carriers and lipophilic antioxidants. The lipophilic carriersdisclosed herein are selected to maximize solubility of the lipophilicantioxidants while concurrently minimizing any chemical degradation ofthe lipophilic antioxidants. For example, in certain aspects, thelipophilic antioxidants are completely solubilized or are solubilized tono less than 98%, 98.5%, 99%, or 99.5% with the disclosed emulsions andbalms such that the lipophilic antioxidant does not visibly precipitateout of the balms and emulsions. With regard to the disclosed balms andemulsions, the liphophilic carriers are selected to maximize potency andefficacy of the lipophilic antioxidant. Additionally, the lipophiliccarriers are selected to maximize skin penetration efficacy. In otherwords, the lipophilic carriers allow for efficient penetration of asubject's epidermis and dermis while concurrently minimizing anychemical degradation of the lipophilic antioxidants. Also, it ispreferred that the lipophilic carriers are pharmaceutically acceptablecarriers.

Within the disclosed balms and emulsions, the lipophilic carrier andlipophilic antioxidant(s) are present at a ratio ranging from 1:1 to25:1, 1:1 to 20:1, 1:1 to 15:1, 1:1 to 10:1, 1:1 to 5:1, 1:1 to 3:1, or1:1 to 2:1. More preferably, within the disclosed balms and emulsions,the lipophilic carrier and lipophilic antioxidant(s) are present at aratio ranging from 1:1 to 10:1. Most preferably, within the disclosedbalms and emulsions, the lipophilic carrier and lipophilicantioxidant(s) are present at a ratio ranging from 1:1 to 5:1. Theseabove discussed ratios are preferred because the solution is stable andeffective, and when the lipophilic carrier and lipophilic antioxidant(s)are used in ratios outside of those disclosed above, precipitation ofsolids and/or loss of efficacy disadvantageously occurs.

In certain aspects, the lipophilic carrier ranges from 50-99 wt %, 60-98wt %, 75-98 wt %, 85-98 wt %, 95-99 wt %, 96-99 wt %, or 96-98 wt % forbalm, and 1-50 wt %, 2-40 wt %, 5-35 wt %, 7.5-25 wt % for emulsions ofthe overall composition. More preferably, the lipophilic carrier rangesfrom 17-99 wt % for balm, and 5-30 wt % for emulsions of the overallcomposition. Most preferably, the lipophilic carrier ranges from 90-98wt % for balm and 10-20 wt % for emulsions of the overall composition.The lipophilic weight percentages above are preferred becauseconcentrations of antioxidant above these percentage do not yieldincreased efficacy, and when the lipophilic carrier (in combination withthe lipophilic antioxidant(s)) is provided in a weight percentagefalling outside of those above disclosed ranges, precipitation and orloss of efficacy disadvantageously occurs.

In certain aspects, the lipophilic carriers advantageously include waxesand/or oils that solvate the lipophilic antioxidants while maintainingthe chemical activity of lipophilic antioxidants. It is desired for thefinal product to have a solid or semisolid consistency. Thereforethicker oils and hydrogenated oils, or butters, are preferred. Incertain aspects, antioxidant potency and/or efficacy is diminished whenthe antioxidant is mixed with high molecular weight carriers having amolecular weight (Mw) ranging from 150 to 600, from 200 to 550, from 250to 500, from 250 to 475, from 250 to 400, from 250 to 350, from 300 to475, from 350 to 450, and from 400 to 450. In certain aspects, thelipophilic carrier is as beeswax having a molecular weight ranging from300 to 475, from 350 to 450, or from 400 to 430. In certain aspects, thelipophilic carrier may include avocado butter having a molecular weightranging from 200 to 350, from 215 to 300, from 240 to 290, or from 260to 290. In certain aspects, these lipid carriers included within thedisclosed formulations can include mineral oils, saturated vegetableoil, unsaturated vegetable oil, or a combination thereof. In certainaspects, it is preferable that the emulsion and balms include one ormore of the disclosed lipophilic carriers. In certain aspects, it ispreferable that the emulsions and balms include at least two of thedisclosed lipophilic carriers. In yet another aspect, it is preferablethat the emulsions and balms include three or more of the disclosedlipophilic carriers.

Examples of vegetable oils may include, but are not limited to, arganoil, avocado oil, babassu oil, canola oil, coconut oil, hemp seed oil,jojoba oil, olive oil, and rosehip oil. In certain aspects, thelipophilic carrier includes at least one vegetable oil selected fromargan oil, avocado oil, babassu oil, canola oil, coconut oil, hemp seedoil, jojoba oil, olive oil, and rosehip oil. In certain aspects, thelipophilic carrier includes at least two vegetable oils selected fromargan oil, avocado oil, babassu oil, canola oil, coconut oil, hemp seedoil, jojoba oil, olive oil, and rosehip oil. In certain aspects thesaturated vegetable oils can include butters, which have a higherviscosity than unsaturated oils and are typically solid or semi-solidsat room temperature. Examples of saturated oils include, but are notlimited to, avocado butter, mango butter, shea butter, cocoa butter, andany combination thereof. In certain aspects, it is advantageous to usethe unsaturated vegetable oils in the disclosed emulsions because oftheir lower viscosities (in comparison to the disclosed butters andwaxes). However, it is advantageous to use the saturated oils in thebalms due their higher viscosities (in comparison to the disclosedbutters and waxes).

Examples of mineral oils may include, but are not limited to, alkanebased oils having, preferably, ranging from C₁₅ to C₄₀ in length (e.g.,C_(n)H_(2n+1)). In certain aspects, the mineral oils are petroleum baseddistillates that include, for example, paraffinic oils, naphthenic oils,and combinations thereof. Specific examples of paraffinic oils caninclude mineral oil, petroleum jelly and paraffin wax. In certainaspects, the balms and emulsions can include two or more paraffinicoils. In certain aspects, the balms and emulsions can include three ormore paraffinic oils. In certain aspects, the balms and emulsions caninclude two or more naphthenic oils. In certain aspects, the balms andemulsions can include three or more naphthenic oils. The paraffinic andnaphthenic oils disclosed herein preferable include a viscosity rangingfrom 0.5 to 2000 cP, 50 to 1500 cP, 200 to 1250 cP, 500 to 1000 cP, or750 to 900 cP when included within the emulsions and balms.

As stated above, the disclosed lipophilic carriers solubilize thelipophilic antioxidants provided within the balms and emulsions. Incertain aspects, the lipophilic antioxidants include at least onephenolic compound, and in a most preferred aspect, these lipophilicantioxidant may include at least one sterically hindered phenol(hereafter “hindered phenols”). Hindered phenols are primaryantioxidants that act as hydrogen donors to effectively neutralize ROS(e.g., free radicals) thereby preventing or reducing the possibility ofROS inducing a deleterious cellular process. In certain aspects, it isadvantageous to include the hindered phenols within the balms andemulsion due the chemical nature of these compounds. Specifically,hindered phenols are lipophilic, hydrophobic compounds that can beabsorbed by biological membranes having high lipid content (e.g.,membranes in the epidermis and dermis). By providing easy absorptionthrough these biological membranes, these antioxidants can also beefficiently absorbed into the blood stream while maintaining a highamount of chemical activity. Thus, the hindered phenols areadvantageously included in the disclosed balms and emulsions topotentially reduce intracellular ROS and to potentially treat variousmaladies including unwanted skin conditions, such as roseacea,psoriasis, acne, eczema, diaper rash, keloid scarring, and combinationsthereof.

In certain aspects, the lipophilic antioxidants are included from 0.25to 50 wt %, 1 to 45 wt %, 1 to 30 wt %, 1 to 10 wt %, 1 to 5 wt %, 1 to3 wt %, 5 to 40 wt %, 5 to 30 wt %, or 10 to 20 wt % of the overallcomposition. More preferably, the lipophilic antioxidants are includedfrom 1 to 10 wt % of the overall composition. Most preferably, thelipophilic antioxidants are included from 2 to 4 wt % of the overallcomposition. The lipophilic antioxidant weight percentages above arepreferred because addition of more antioxidant, particularly fallingoutside the preferred and most preferred ranges, will not improveproduct efficacy, but will instead only increase manufacturing cost.When the lipophilic carrier (in combination with the lipophilicantioxidant(s)) is provided in a weight percentage falling outside ofthose above disclosed ranges, precipitation and or loss of efficacydisadvantageously occurs.

The lipophilic antioxidant includes one of the following formulas (I) to(III):

wherein,

R₁ represents a C₁ to C₉ linear or branched alkyl group, styrene, or H;

R₂ is optional and represents a C₁ to C₆ linear or branched alkyl group,styrene, or H;

Y₁ represents a C₁ to C₆ linear or branched alkyl group, styrene, —SR₅,or —(CH₂)_(n)COOR₆;

R₃ and R₄ independently represent a C₁ to C₆ branched alkyl or H;

Y₂ represents a C₁ to C₆ linear or branched alkyl group, —SR₅,—(CH₂)_(n)COOR₆, or H;

Y₃ represents a linear or branched alkyl group or H;

In certain aspects, n is from 1 to 10, 1 to 5, 1 to 3, 2 to 6, or 3 to7. In certain aspects, it is preferable that the compounds arepharmaceutically acceptable compounds or salts thereof.

With regard to Formula I, OH, Y₁, R₁, and R₂ can be in the ortho, meta,and para positions relative to each other.

In certain aspects, the C₁ to C₉ linear or branched alkyl group of R₁,and the C₁ to C₆ linear or branched groups of R₂, R₃, R₄, Y₁, Y₂, and Y₃can independently represent, for example, a methyl group, an ethylgroup, a propyl, a butyl, a pentyl group, a hexyl group, an isopropylgroup, an isobutyl group, a sec-butyl group, a tert-butyl group, atert-pentyl group, a neo-pentyl group, an isopentyl group, an isohexylgroup, or a neohexyl group. In certain aspects, the C₁ to C₉ group of R₁is a nonyl group. In certain aspects, the C₁ to C₆ linear or branchedalkyl groups of Y₁ and Y₂ may be substituted with:

wherein R7 represents

wherein R₈, R₉, and R₁₀ independently represent OH, a methyl group,ethyl group, a propyl group, a butyl group, an isopropyl group, atert-butyl group, an isoprene, or a tert-pentyl group, wherein at leastone of R₈, R₉, and R₁₀ is OH. R₈, R₉, and R₁₀ can be in any of theortho, meta, and para positions relative to each other.

In certain aspects and as defined herein, styrene of R₁, R₂, and Y₁ caninclude substituted benzene and independently represents

In certain aspects, R₅ represents a C₁ to C₃₀ linear or branched alkylgroup or a substituted or unsubstituted aryl group. In certain aspects,R₅ represents isoprene, a methyl group, an ethyl group, a propyl, abutyl, a pentyl group, a hexyl group, an isopropyl group, an isobutylgroup, a sec-butyl group, a tert-butyl group, a tert-pentyl group, aneo-pentyl group, an isopentyl group, an isohexyl group, or a neohexylgroup. In certain aspects, R₅ represents,

wherein R₁₁, R₁₂, and R₁₃ independently represent OH, a methyl group,ethyl group, a propyl group, a butyl group, an isopropyl group, atert-butyl group, an isoprene, or a tert-pentyl group, wherein at leastone of R₁₁, R₁₂, and R₁₃ is OH. R₁₁, R₁₂, and R₁₃ can be in any of theortho, meta, and para positions relative to each other.

In certain aspects, Y₃ represents an alkyl group having C₁₀ to C₃₀. Incertain aspects, this C₁₀ to C₃₀ alkyl group may be saturated orunsaturated and may be linear or branched. In certain aspects, it ispreferred that this C₁₀ to C₃₀ alkyl group is saturated havingC_(n)H2_(n+1). In certain aspects, it is preferred that Y₃ represents analkyl group having C₁₂ to C₂₀ and is preferably C_(n)H2_(n+1). In mostpreferred aspects, Y₃ represents C₁₅H₃₁, C₁₆, H₃₃, C₁₇H₃₅, C₁₈H₃₇,C₁₉H₃₉, or C₂₀H₄₁.

In certain aspects, the compound disclosed in Formula III can be stereospecific or non-stereo specific. Specifically, the carbon linked to Y₃is an asymmetric center. The compound disclosed in Formula III caninclude a racemic mixture of R, S compounds, only R compounds, or only Scompounds. In certain aspects, it is preferable that the compounds ofFormula III are a racemic mixture of R, S compounds. In certain aspects,it is preferable that the compounds of Formula III are only R compounds.In certain aspects, it is preferable that the compounds of Formula IIIare only S compounds.

Specific examples of the antioxidants from Formula I include, but arenot limited to, the following:

Specific examples of the antioxidants from Formula II include, but arenot limited to, the following:

In certain aspects, the lipophilic antioxidants specifically include atleast one of an isobutylenated methylstyrenated phenol, a styrenatedphenol, various o-, m-, p-cresols (e.g.,4,4′thiobis-6-(t-butyl-m-cresol),4,4′-butylidenebis-b-(t-butyl-m-cresol)), 2,6-di-tert-butyl-p-cresol,(octadecanoxycarbonylether) phenol,tetrakis-(methylene-(3,5-ditertbuty-4-hydrocinnamate)methane,2,2′-methylenebis(4-methyl-6-nonyl) phenol,1,3,5-tris(3,5-di-tert-butyl-4-hydroxybenxyl-)-1,3,5-triazine-2,4,6 (1H,3H, 5H)-trione, and combinations thereof within the emulsions and balms.In certain aspects, the lipophilic antioxidants specifically include atleast two, three, four or five of an isobutylenated methylstyrenatedphenol, a styrenated phenol, various o-, m-, p-cresols (e.g.,4,4′thiobis-6-(t-butyl-m-cresol),4,4′-butylidenebis-b-(t-butyl-m-cresol)), 2,6-di-tert-butyl-p-cresol,(octadecanoxycarbonylether) phenol,tetrakis-(methylene-(3,5-ditertbuty-4-hydrocinnamate)methane,2,2′-methylenebis(4-methyl-6-nonyl) phenol,1,3,5-tris(3,5-di-tert-butyl-4-hydroxybenxyl-)-1,3,5-triazine-2,4,6 (1H,3H, 5H)-trione, and combinations thereof within the emulsions and balms.

Additional skin penetration enhancers including, but not limited to,organic solvents and/or surfactants that aid in penetration of theepidermis and dermis may also be included within the disclosed emulsionsand balms. Examples of organic solvents included within the disclosedformulations may include, but are not limited to, dimethyl sulfoxide,azone (l-dodecylazacycloheptan-2-one or laurocapran) and pyrrolidones(e.g., N-methyl-2-pyrrolidone). Examples of surfactants included withinthe disclosed formulations may include, but are not limited to, linearalkylbenzenesulfonates, lignin sulfonates, fatty alcohol ethoxylates,alkylphenol ethoxylates, various lactate ethers, ethylene glycol,glycerol, propylene glycol, diethylene glycol, dimethyl isosorbide,various fatty acids, including but not limited to, stearic acid,stearates, stearic acid derivatives, palmitic acid, palmitates, palmiticacid derivatives, arachidic acid, arachidic acid derivatives,arachidonic acid, arachidonic acid derivatives, oleic acid, oleic acidderivatives, linolenic acid, linolenic acid derivatives, or anycombination thereof. For example, preferred stearic acid derivativesinclude, but are not limited to, an of Steareth-3, Steareth-5,Steareth-8, Steareth-14, Steareth-16, Steareth-21, Steareth-25,Steareth-27, Steareth-30, Steareth-40, Steareth-50, Steareth-80,Steareth-100, Steareth-200, which are polyethylene glycol ethers ofstearic acid. In certain aspects, the surfactants may include anycombination of Steareth-3, Steareth-5, Steareth-8, Steareth-14,Steareth-16, and Steareth-21. Additional skin penetration enhancersincluded within the disclosed formulations may include urea,oxazolidinones (e.g., 4-decyloxazolidin-2-one), terpenes, andterpenoids. At least one or any combination of the above mentioned skinpenetration enhancers can be included at an overall combinedconcentration ranging from 1 to 10 wt %, more preferably from 2 to 8 wt%, and most preferably from 3 to 5 wt % of the overall composition. Incertain aspects, additives including any combination of aloe vera, aloevera extract, D-Ascorbic Acid, L-Ascorbic Acid, D and L-Ascorbic Acid,glycerin, lilac, and silicone based additives may be included in theemulsion or balm at concentrations ranging from 10 to 40 wt %, 18 to 35wt %, 25 to 35 wt %, or 28 to 32 wt % of the overall composition.

In certain aspects, various preservatives (e.g., stabilizers) andfragrances can be added to increase shelf life of the disclosedformulations, as well as enhancing the aesthetic aroma/smell of theseformulations. In certain aspects, these preservatives, fragrances, orthe combination thereof can be present within the disclosed emulsionsand balms at a concentration of 0.5 to 5 wt %, 0.75 to 3 wt %, 1 to 2 wt% with the preferred concentration being approximately 1%. Fragrancetypes can include botanical derivatives, or manufactured chemicalfragrances, like those used in soap making. Preservatives (e.g.,stabilizers) may include, but are not limited to, formulations havingany combination of the following: propylene glycol, propylparaben,methylparaben, diazolidnyl urea, neem oil, sweet orange oil, potassiumsorbate, benzylalcohol, tetrasodium EDTA, phenoxyethanol, iodopropynyl,and hydantoin. For example, in certain aspects, the preservative,Germaben II, may be included within the disclosed formulations.

Methods of Making Emulsions and Balms

In certain aspects, the disclosed balms may include the lipophiliccarrier and at least one of the lipophilic antioxidants having formulas(I) to (III) disclosed above. When making the disclosed balm, anappropriate amount of the lipophilic carrier and the appropriate amountof the at least one lipophilic antioxidant is weighed out andsubsequently mixed together. In certain aspects, the lipophilic carrieris admixed with at least one lipophilic antioxidant having formulas (I)to (III) and heated at temperatures ranging from 230-275° F., morepreferably from 240-270° F., most preferably from 250-265° F. during atime period from 5-60 min, preferably from 5-15 min, most preferably 5min. In this mixture referred, to as a master batch, the antioxidant tocarrier ratio is very high, for example, approximately a 1:1 ratio byweight in order to solubilize the antioxidant. This mixture will notremain liquid and flow able at room temperature. And only serves todisperse the melted antioxidant into the batch without the need to heatthe entire mass. While heating the admixed lipophilic carrier with thelipophilic antioxidant, the admixture will gradually change from acloudy, precipitous-like appearance to a clear, transparent-likeappearance. During this process it is important that the admixture iscompletely melted so that no solid particles remain. This ensures thatthe lipophilic antioxidant achieves maximum solubilization within thelipophilic carrier. This is important for two reasons, if theantioxidant particles are too large absorption into the skin is notpossible, rendering the product ineffective, and the grainy nature ofthe antioxidant is unpleasant when applied to the skin.

In certain aspects, the admixture having the lipophilic antioxidantsolubilized in the lipophilic carrier may be subsequently added to(e.g., diluted with) an additional lipophilic carrier. This additionallipophilic carrier has also preferably been liquefied before adding theadmixture having the lipophilic antioxidant solubilized in thelipophilic carrier. For example, in certain aspects, this additionallipophilic carrier may be a liquefied lipophilic carrier (or a heatedoil) contained within an industrial, pharmaceutical-type melt tank. Inpreferred embodiments, the melt tank has been warmed long enough and toa temperature sufficient to liquefy and/or heat the lipophilic carrier,but not warm enough to boil or flash off the lipophilic carrier. Incertain aspects, the industrial, pharmaceutical-type melt tank may bepre-warmed. In certain aspects, the industrial, pharmaceutical-type melttank has been warmed to a temperature of 100-150° F. preferably 110-130°F., most preferably 120° F. It preferable not to exceed 150° F. toprevent separation of the hydrogenated oil (e.g., avocado butter) fromthe other ingredients. If heated too long or too hot the butter takes onan unpleasant consistency. In certain aspects, this additionallipophilic carrier may be the same or a different lipophilic carrierthan what has been used in the admixture, and in certain aspects, theadditional lipophilic carrier may further include additional solvents,surfactants, oils, lipophilic antioxidants having formulas (I) to (III)as disclosed above, or any combination thereof.

As discussed above, the admixture having the lipophilic antioxidantsolubilized in the lipophilic carrier is subsequently added to (e.g.,diluted) in the additional lipophilic carrier and mixed for 5-60minutes, more preferably 10-30 minutes, and most preferably 20 minuteswhile concurrently being heated to ensure overall homogeneity. Duringthis mixing step, fragrance can optionally be added to provide theresulting balm with the desired fragrance. In certain aspects, theresulting mixture can be discharged from the industrial,pharmaceutical-type melt tank into appropriate receptacles (e.g.,plastic jars) and allowed to cool and subsequently harden, thusresulting in the disclosed balms.

The emulsion is made by substantially the same process as disclosedabove. However, the emulsion further includes a surfactant allowing theoil phase along with the antioxidant and water phase to be properlymixed. In certain aspects, all of the water based ingredients are mixedtogether and heated to approximately 150° F. Similarly, the oil basedingredients and the surfactants are heated and mixed together. Then onceboth parts, known as phases, are heated and mixed then they are combinedwith each other while mixing to form the emulsion. Generally the mixingoccurs for the duration of the cool down and the mixer generally iscapable of generating high shear forces.

In certain aspects, the disclosed balm may be made without heat and bymerely using mechanical means to mix the ingredients (e.g., carrier oil,antioxidant, etc.) to reduce particle size such that the balm mayeffectively penetrate skin. For example, the following two methods maybe used. The first method involves tumbling the ingredients in a sealedcontainer. For example, a liquid tight rotary tumbler may be used, andthe tumbling media used is stainless steel ball bearings. In thisaspect, the antioxidant powder is weighed out as well as the carrieroil. In certain aspects, Vitamin E oil may also be used. With thismethod, the ingredients (e.g., lipophilic carrier and antioxidant) areplaced into the tumbler at an acceptable ratio of 1:1 to 20:1, morepreferably 1:1 to 5:1 and most preferably 1:1. The tumbler, when loadedwith media and all ingredients, should be approximately ¾ full. Thetumbler is turned on and the barrel turns for approximately 12 hours. Incertain aspects, the agitation rate ranges from 30 to 80 rpm, 40 to 70rpm, and 50 rpm to 65 rpm, and 55 rpm to 65 rpm. During this time, theball bearings pulverize the powder and reduce the particle sizesignificantly. The final product has been tested and will pass through a325 mesh screen and have a particle diameter ranging from 30 nm to 30μm, 30 nm to 15 μm, 40 nm to 10 μm, 40 nm to 5 μm, 40 nm to 1 μm, 40 nmto 900 nm, 40 nm to 750 nm, 40 nm to 500 nm, 50 nm to 400 nm, 40 nm to300 nm, 50 nm to 250 nm, 40 nm to 100 nm, and 40 nm to 70 nm. The ballbearings are separated from the mixture with a sieve and cleaned forreuse.

The second mechanical method involves the use of a high shear mixer,which includes, for example, a Vertishear Tempest machine. Theingredients, which include a powder form of the antioxidant and thecarrier oil, are added to an appropriately sized container at a ratio of1:1 by weight. Similar to the previously described mechanical method,Vitamin E oil may also be used. The mixture is processed in the mixerfor approximately 2 hours. It is important to note that the speed of themixer should be limited. Due to the friction between the solid particlesand the high speed mixing blade, heat will be generated. It is importantto limit this heat to below 200° F. Otherwise the antioxidant particleswill start to melt and fuse together creating a hardened mass that willnot mix. In order to avoid this, the speed of the mixer should becontrolled, or the mixing performed in cycles allowing the mixture tocool intermittently.

WORKING EXAMPLES

The following discloses an exemplary balm made according to the methodsand compositions disclosed herein.

Example 1: Exemplary Balm

1.1 Materials Used

-   -   1.1.1 Avocado Butter glorybeefoods.com    -   1.1.2 IRGANOX® 1010 BASF, having the chemical name        Pentaerythritol        tetrakis(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate) having        a molecular weight of 1178 g/mol as specified in BASF's plastic        additive's “Technical Information” sheet from September 2010,        CAS No. 6683-19-8.    -   1.1.3 Vitamin E Oil lotioncrafter.com    -   1.1.4 Fragrance currently using cucumber melon fragrance sourced        from soaperafter.com    -   1.1.5 Scale    -   1.1.6 Double Boiler    -   1.1.7 Plastic tamper seal plastic shrink bands provided by        sks-bottle.com

Ingredient Full Batch Qty. % Avocado Butter 15 lbs. (240 oz.) 94Irganox ® 1010 7.65 oz. 3 Vitamin E Oil 7.65 oz. 3 Fragrance 2 TBSP1.2 Weighing of Raw Materials

-   -   NOTE all raw material containers must be sealed at all times and        are only opened while in use.    -   NOTE: ALL materials acceptable variation is ±0.1 Unit of        Measurement.

1.2.1 Avocado Butter

-   -   1.2.1.1 Using “OHAUS® CD-II” scale, be sure that scale is        displaying the “oz.”, (ounces) setting.    -   1.2.1.2 Zero out the scale by pressing the “tare” button.    -   1.2.1.3 Weighed out the correct amount of Avocado butter, and        placed into the storage container.

1.2.2 Irganox® 1010 Antioxidant and Vitamin E Oil

-   -   1.2.2.1 Using “OHAUS® CD-II” scale, be sure that scale is        displaying the “oz.”, (ounces) setting.    -   1.2.2.2 Zero out the scale by pressing the “tare” button.    -   1.2.2.3 Weighed out the correct amount of IRGANOX® 1010 and        place into tumbling canister.    -   1.2.2.4 Weigh out the correct amount of Vitamin E Oil and place        into a tumbling canister.    -   1.2.2.5 Tumble for 12 hours and place into sealed storage        container. This will now be referred to as the “Antioxidant        Master Batch.”        1.3 Heating Material in Double Boiler    -   1.3.1 Pre-heat double boiler to 150° F.    -   1.3.2 Add the measured Avocado butter and Antioxidant Master        Batch. Mix thoroughly.    -   1.3.3 Add fragrance and mix.    -   1.3.4 Pour contents into dispensing container.

Example 2: Exemplary Emulsion/Lotion

1.0 Materials Used

Units (g) Percentage (Wt %) 1.1 Part 1 Water Based Ingredients 1.1.1Distilled Water 2020.00 51.53% 1.1.2 Glycerin 400.00 10.20% 1.2 Part 2Oil Based Ingredients 1.2.1 I-Butter 280.00 7.14% (IRGANOX ® 1010 BASF &Avocado butter) 1.2.2 Stearic Acid 120.00 3.06% 1.2.3 Mineral oil(Lilac) 400.00 10.20% 1.2.4 Sonnecone Petrolatum 400.00 10.20% 1.2.5Vitamin E 80.00 2.04% 1.2.6 Steareth 2 91.72 2.34% 1.2.7 Steareth 2148.28 1.23% 1.3 Part 3 Cream stabilizer and preservative 1.3.1GERMABEN ® II 10.00 0.25% 1.3.2 Fragrance 70.00 1.78% Overall Totals:3920.00 100.00% GERMABEN ® II manufactured by Sutton Laboratories havingCAS Registry No. 57-55-6; 78491-02-8; 99-76-3; 94-13-3 having 56 wt %1,2-Propanediol (57-55-6) and 30 wt %Urea(N-(1,3-bis(hydroxymethyl)-2,5-dioxo-4-imidazolidinyl)-N,N′-bis(hydroxymethyl)(78491-02-8).2.0 Procedure

-   -   2.1 All batches were made by weight percentage ratios.    -   2.2 Heated up the I 1010 and Avocado Butter in correct weight        percentage ratios (e.g., a        -   2.5:1 I 1010:Avacado Butter, or more preferably a 3:1 ratio            of Avocado Butter:I 1010) to produce I-Butter.            -   2.2.1 Kept on low heat and set aside for Part 2 mixture.    -   2.3 Part 1 Mixture        -   2.3.1 Using cooking scale measured out all ingredients for            Part 1 Water Based Ingredients based off of Percent            composition shown in 1.1 above.        -   2.3.2 Add all ingredients to heated container and mix            thoroughly            -   2.3.2.1 Part 1 Water Based Ingredients are heated and                mixed to between 150° F.-200° F. without allowing Part 1                to boil    -   2.4 Part 2 Mixture        -   2.4.1 Measured out all ingredients for Part 2 Oil Based            Ingredients based off of Percent composition shown in 1.2            above.        -   2.4.2 Added all ingredients to a separate heated container            and mixed thoroughly            -   2.4.2.1 Made sure to heat all granules to a liquid in                the Part 2 mixture, failure to do so will result in                grainy lotion cream leading to a defective product            -   2.4.2.2 Part 2 Oil Based Ingredients were heated and                mixed to between 150° F.-200° F. without allowing Part 2                to boil.    -   2.5 Part 3 Mixture        -   2.5.1 Using cooking scale measured out all ingredients for            Part 3 Cream stabilizer and preservative based off of            Percent composition shown in 1.3 above.        -   2.5.2 Combined the two ingredients and placed to the side    -   2.6 Combining Mixtures Parts 1, 2, and 3        -   2.6.1 After Parts 1 and 2 have reached a temperature ranging            from between 150° F.-200° F.        -   2.6.2 Combined Part 1 and 2 mixtures together. Thoroughly            blended the two mixtures together in the homogenizer at            2,800 rpm.        -   2.6.3 New mixture containing Part 1 and 2 must reach a            temperature below 150° F., continuously mixed new mixture            until temperature was attained        -   2.6.4 Once the mix has reached 160° F. add Part 3 while            continuing to mix.        -   2.6.5 Place the mix from the previous step into the            homogenizer at 2,800 rpm until there was no frothy head of            foam on top of lotion and then dispensed into appropriate            container, approximately 30 minutes.        -   2.6.6 Add the mixture from part 3 to the homogenizer and mix            for 30 minutes at 2,800 rpm.

The foregoing description provides embodiments of the invention by wayof example only. It is envisioned that other embodiments may performsimilar functions and/or achieve similar results. Any and all suchequivalent embodiments and examples are within the scope of the presentinvention and are intended to be covered by the appended claims.

What is claimed is:
 1. An emulsion for topical application comprising: awater phase ranging 60-90% of the overall emulsion, and an oil phase,wherein: the oil phase comprises a lipophilic carrier, a skinpenetration enhancer, an additive selected from the group consisting ofaloe vera extract, D-Ascorbic Acid, L-Ascorbic Acid, D and L-AscorbicAcid solution, glycerin, lilac, and silicone, the additive ranging frommore than 18% to 40% of the overall emulsion, and a lipophilicantioxidant solubilized by the lipophilic carrier and forming asuspension, the lipophilic carrier and the lipophilic antioxidant beingpresent from 1:1 to 20:1 of lipophilic carrier to lipophilic antioxidantin the emulsion, the lipophilic antioxidant having been powderized to aparticle diameter size selected from the group consisting of 40 nm to 5μm, 40 nm to 1 μm, 40 nm to 900 nm, 40 nm to 750 nm, 40 nm to 500 nm, 50nm to 400 nm, 40 nm to 300 nm, 50 nm to 250 nm, 40 nm to 100 nm, and 40nm to 70 nm prior to being solubilized by the lipophilic carrier, andthe lipophilic antioxidant having one of the following formulas (I) to(III):

wherein: R₁ represents a C₁ to C₉ linear or branched alkyl group orstyrene; R₂ is optional and represents a C₁ to C₆ linear or branchedalkyl group or styrene; Y₁ represents a C₁ to C₆ linear or branchedalkyl group, styrene, —SR₅, or —(CH₂)_(n)COOR₆; R₃ and R₄ independentlyrepresent a C₁ to C₆ branched alkyl; Y₂ represents a C₁ to C₆ linear orbranched alkyl group, —SR₅, or —(CH₂)_(n)COOR₆; Y₃ represents a linearor branched alkyl group; n is from 1 to 10; R₅ represents isoprene, amethyl group, an ethyl group, a propyl, a butyl, a pentyl group, a hexylgroup, an isopropyl group, an isobutyl group, a sec-butyl group, atert-butyl group, a tert-pentyl group, a neo-pentyl group, an isopentylgroup, an isohexyl group, a neohexyl group, styrene, or

wherein R₁₁, R₁₂, and R₁₃ independently represent OH, a methyl group,ethyl group, a propyl group, a butyl group, an isopropyl group, atert-butyl group, an isoprene, or a tert-pentyl group, and R₆ representsan alkyl group having C₁₀ to C₃₀; and wherein formulas (I) to (III)include pharmaceutically acceptable salts thereof.
 2. The emulsion ofclaim 1, wherein the C₁ to C₆ linear or branched alkyl groups of Y₁ andY₂ are substituted with

wherein: R₇ represents

wherein: R₈, R₉, and R₁₀ independently represent OH, a methyl group,ethyl group, a propyl group, a butyl group, an isopropyl group, atert-butyl group, an isoprene, or a tert-pentyl group; at least one ofR₈, R₉, and R₁₀ is OH; and R₈, R₉, and R₁₀ can be in any of the ortho,meta, and para positions relative to each other.
 3. The emulsion ofclaim 1, wherein the emulsion includes at least two lipophilicantioxidants from formulas (I) to (III).
 4. The emulsion of claim 1,wherein the emulsion includes at least three lipophilic antioxidantsfrom formulas (I) to (III).
 5. The emulsion of claim 1, wherein thelipophilic carrier and the lipophilic antioxidant are present from 1:1to 10:1 of lipophilic carrier to lipophilic antioxidant in the emulsion.6. The emulsion of claim 1, wherein the lipophilic carrier and thelipophilic antioxidant are present from 1:1 to 1:5 of lipophilic carrierto lipophilic antioxidant in the emulsion.
 7. The emulsion of claim 1,wherein the oil phase ranges from 10 wt % to 40 wt % of the overallemulsion.
 8. The emulsion of claim 5, wherein the oil phase ranges from10 wt % to 40 wt % of the overall emulsion.
 9. The emulsion of claim 1,wherein the lipophilic carrier comprises at least one of a mineral oil,vegetable oil, or combinations thereof.
 10. The emulsion of claim 9,wherein the mineral oil is a paraffinic oil.
 11. The emulsion of claim9, wherein the mineral oil is a naphthenic oil.
 12. The emulsion ofclaim 1, wherein the lipophilic carrier includes at least one selectedfrom the group consisting of argan oil, avocado oil, babassu oil, canolaoil, coconut oil, hemp seed oil, jojoba oil, olive oil, and rosehip oil.13. The emulsion of claim 1, wherein the lipophilic carrier is avocadobutter, mango butter, shea butter, cocoa butter, or any combinationthereof.
 14. A method for making an emulsion for topical applicationcomprising: providing water and a vegetable or mineral oil, providing apowdered lipophilic antioxidant having a particle diameter size selectedfrom the group consisting of 40 nm to 5 μm, 40 nm to 1 μm, 40 nm to 900nm, 40 nm to 750 nm, 40 nm to 500 nm, 50 nm to 400 nm, 40 nm to 300 nm,50 nm to 250 nm, 40 nm to 100 nm, and 40 nm to 70 nm, and mixing thewater and the vegetable or mineral oil with a surfactant to form theemulsion, wherein the emulsion includes: a water phase ranging 60-90% ofthe overall emulsion, and an oil phase, wherein: the oil phase comprisesa lipophilic carrier, a skin penetration enhancer, an additive selectedfrom the group consisting of aloe vera extract, D-Ascorbic Acid,L-Ascorbic Acid, D and L-Ascorbic Acid solution, glycerin, lilac, andsilicone, the additive ranging from more than 18% to 40% of the overallemulsion, and a lipophilic antioxidant solubilized by the lipophiliccarrier forming a suspension, the lipophilic carrier and the lipophilicantioxidant being present from 1:1 to 1:20 of lipophilic carrier tolipophilic antioxidant in the emulsion, and the lipophilic antioxidanthaving one of the following formulas (I) to (III):

wherein, R₁ represents a C₁ to C₉ linear or branched alkyl group orstyrene; R₂ is optional and represents a C₁ to C₆ linear or branchedalkyl group or styrene; Y₁ represents a C₁ to C₆ linear or branchedalkyl group, styrene, —SR₅, or —(CH₂)_(n)COOR₆; R₃ and R₄ independentlyrepresent a C₁ to C₆ branched alkyl; Y₂ represents a C1 to C₆ linear orbranched alkyl group, —SR₅, or —(CH₂)_(n)COOR₆; Y₃ represents a linearor branched alkyl group; n is from 1 to 10; R₅ represents isoprene, amethyl group, an ethyl group, a propyl, a butyl, a pentyl group, a hexylgroup, an isopropyl group, an isobutyl group, a sec-butyl group, atert-butyl group, a tert-pentyl group, a neo-pentyl group, an isopentylgroup, an isohexyl group, a neohexyl group, styrene, or

wherein R₁₁, R₁₂, and R₁₃ independently represent OH, a methyl group,ethyl group, a propyl group, a butyl group, an isopropyl group, atert-butyl group, an isoprene, or a tert-pentyl group, R₆ represents analkyl group having C₁₀ to C₃₀; and wherein formulas (I) to (III)included pharmaceutically acceptable salts thereof.
 15. The method ofclaim 14, wherein the water and the vegetable or mineral oil with thesurfactant are mixed at a temperature ranging from 100° F. to 150° F.for 5 to 60 minutes to form the emulsion.
 16. A balm for topicalapplication comprising: a lipophilic carrier, a skin penetrationenhancer, an additive selected from the group consisting of aloe veraextract, D-Ascorbic Acid, L-Ascorbic Acid, D and L-Ascorbic Acidsolution, glycerin, lilac, and silicone, the additive ranging from morethan 18% to 40% of the overall emulsion, and a lipophilic antioxidantsolubilized by the lipophilic carrier forming a suspension, thelipophilic carrier and the lipophilic antioxidant being present from 1:1to 1:20 of lipophilic carrier to lipophilic antioxidant in the emulsion,the lipophilic antioxidant having been powderized to a particle diametersize selected from the group consisting of 40 nm to 5 μm, 40 nm to 1 μm,40 nm to 900 nm, 40 nm to 750 nm, 40 nm to 500 nm, 50 nm to 400 nm, 40nm to 300 nm, 50 nm to 250 nm, 40 nm to 100 nm, and 40 nm to 70 nm priorto being solubilized by the lipophilic carrier, and The lipophilicantioxidant having one of the following formulas (I) to (III):

wherein, R₁ represents a C₁ to C₉ linear or branched alkyl group orstyrene; R₂ is optional and represents a C₁ to C₆ linear or branchedalkyl group or styrene; Y₁ represents a C₁ to C₆ linear or branchedalkyl group, styrene, —SR₅, or —(CH₂)_(n)COOR₆; R₃ and R₄ independentlyrepresent a C1 to C6 branched alkyl; Y₂ represents a C₁ to C₆ linear orbranched alkyl group, —SR₅, or —(CH₂)_(n)COOR₆; Y₃ represents a linearor branched alkyl group; n is from 1 to 10; R₅ represents isoprene, amethyl group, an ethyl group, a propyl, a butyl, a pentyl group, a hexylgroup, an isopropyl group, an isobutyl group, a sec-butyl group, atert-butyl group, a tert-pentyl group, a neo-pentyl group, an isopentylgroup, an isohexyl group, a neohexyl group, styrene, or

wherein R₁₁, R₁₂, and R₁₃ independently represent OH, a methyl group,ethyl group, a propyl group, a butyl group, an isopropyl group, atert-butyl group, an isoprene, or a tert-pentyl group, R₆ represents analkyl group having C₁₀ to C₃₀; and wherein formulas (I) to (III) includepharmaceutically acceptable salts thereof.
 17. The emulsion of claim 1,wherein the skin penetration enhancer is an organic solvent.
 18. Themethod of claim 14, wherein the skin penetration enhancer is an organicsolvent.
 19. The balm of claim 16, wherein the skin penetration enhanceris an organic solvent.